report one,
A synthetic method of (S)-(+)-3-hydroxytetrahydrofuran, comprising the following steps:
(1) Add 250g (1.86mol) L-malic acid and 500ml methanol into a 1000ml four-neck reaction flask, turn on stirring, add 20g (0.1mol) concentrated sulfuric acid, after the addition of materials, open condensed water, oil bath 75 ℃, under reflux The reaction was carried out for 2 hours, and the sample was sent to the gas phase to detect the completion of the reaction. After cooling to room temperature, sodium carbonate was added to adjust the pH to 8. The methanol was removed under reduced pressure, and 100 ml of water was added. Afterwards, check whether the water phase has been extracted cleanly, if not, extract it once more with 100ml of dichloromethane, combine the organic phases, remove the solvent under reduced pressure, and steam out 277g of L-dimethyl malate, with a yield of 92%;
(2) Add 100ml of tetrahydrofuran into a 500ml four-necked reaction flask, add 4.663g (0.123mol) of sodium borohydride under stirring, open the condensed water, and then slowly drop 10g (0.0617mol) of L-dimethyl malate into the reaction flask In the bottle, the dripping is completed, the oil bath is heated and refluxed, 20 ml of methanol is added dropwise to the reaction solution under reflux, the dripping is completed, the reflux is stirred for 2 hours, the sampling is completed to detect the reaction, and it is cooled to room temperature to obtain a mixed solution, and then 500 ml of anhydrous ethanol is added. In a 1000ml four-neck reaction flask, start stirring, pour the mixture into absolute ethanol, slowly add 15g (0.15mol) phosphoric acid dropwise, stir at room temperature for 25min, filter, and rinse the filter cake with absolute ethanol 3 times, 20ml each time , the organic phases were combined, and the solvent was removed under reduced pressure to obtain 5.8 g of crude chiral 1,2,4-butanetriol with a yield of 90%;
(3) Add the obtained crude chiral 1,2,4-butanetriol into a vacuum distillation device, heat up to 120°C for self-reaction, and steam (S)-(+)-3-hydroxytetrahydrofuran and water under reduced pressure. The mixture was then dehydrated under reduced pressure at a temperature of 76 °C to obtain 2.4 g of (S)-(+)-3-hydroxytetrahydrofuran with a yield of 45% and an optical purity >99% ee (by chiral gas chromatography Sure).
report two,
Preparation of L-dimethyl malate 2: Dissolve 30g L-malic acid (0.224mol) in 90ml methanol, cool to -10°C, add 39ml thionyl chloride (0.55mol) dropwise with stirring, and finish adding dropwise in 1.5h . Stir at room temperature for 4 h, and then heat to reflux for 1 h to stop the reaction. Concentrate under reduced pressure, add 125 ml of 20% sodium carbonate solution to adjust pH=7.Filter three times, 100ml each time The ethyl acetate layers were combined, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 33.68 g of a colorless oily liquid with a yield of 93%.
Preparation of butanetriol 3: 32.4g L-dimethyl malate (0.2mol) was dissolved in 100ml methanol, 8.48g potassium borohydride (0.16mol) and 17g lithium chloride (0.4mol) were added, and the mixture was heated to reflux. Thereafter, 4.24g potassium borohydride (0.08mol) was added every 20min for a total of 5 times. After the addition was completed, reflux was continued for 3h, and no starting material was detected by TLC, and the reaction was stopped. A large amount of solid was removed by filtration first, the filtrate was adjusted to pH 3 with sulfuric acid, the precipitated solid was removed by filtration again, and concentrated under reduced pressure. The resulting solid-liquid mixture was diluted with 20 ml of ethyl acetate and 20 ml of ethanol, stirred and filtered. The filtrate was concentrated under reduced pressure to obtain 21 g of yellow viscous liquid.
Preparation of (S)-(+)-3-hydroxytetrahydrofuran 4: The crude product obtained in the previous step was added to 2 g (0.01 mol) of p-toluenesulfonic acid monohydrate, heated to dissolve, and the temperature was continued to rise to 200°C. Fractional distillation under reduced pressure (87° C./22 mmHg) collected 7.6 g of yellow oily liquid with a two-step yield of 43%.
